Fight Aging! Newsletter, January 20th 2014

January 20th 2014

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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  • SENS Research Foundation News and 2014 Summer Scholar Program
  • Philanthropist Jason Hope Endorses the SENS Research Foundation's Work on Rejuvenation Biotechnology
  • Recent News in Stem Cell Research
  • A Look Back at 2013 From Methuselah Foundation
  • It Comes Time for the Next Wave of Advocacy and Initiatives in Longevity Science
  • Latest Headlines from Fight Aging!
    • Investigating Tiron, a Mitochondrially Targeted Antioxidant
    • Arguing a Limit on Life Span
    • Proposing Slow Metabolism to Explain Primate Longevity
    • Spurring Cartilage Growth By Mimicking the Response to Physical Activity
    • Digging in to the Epigenetics of Rapamycin-Induced Longevity
    • Telomere Biology in Arctica Islandica
    • Less Sitting and More Exercise Lowers Risk of Chronic Disease
    • A Profile of Scientific Crowdfunding Platform Microryza
    • Boosting Chaperone-Mediated Autophagy to Treat Parkinson's Disease
    • More Evidence for Gut Bacteria to Influence Aging


The latest mail from the SENS Research Foundation notes that the doors are open for students to apply to the 2014 Summer Scholar Program. Talented students studying molecular biology and regenerative medicine have a chance to advance their career prospects while working on cutting edge projects: you can see some of the work accomplished by past interns at the Foundation as an example of this type of program.

Keeping an eye on the long term, this is one of the important organizational Foundation projects. Building rejuvenation biotechnologies is a project of a few decades even if fundraising and persuasion goes well. Those researchers at the peak of their careers who will lead the final stages of work on first generation rejuvenation therapies are still in school today - and public perceptions of biogerontology remain far from what they should be. It is still very necessary here and now to demonstrate to younger researchers in the life sciences that biogerontology is not a boring niche, but rather the exciting, barnstorming, revolutionary early years of the next generation of medicine. This presently small field will grow to dominate and define the mainstream of medical research and development by the 2030s and beyond - a showcase for all the best and brightest applications of molecular biology, genetic engineering, cell therapies, and other presently young fields. Opportunities for achievement, scientific fame, wealth, and the saving of lives on a grand scale will abound in the years ahead.

2014 SRF Summer Scholar Applications Are Here

SENS Research Foundation is proud to offer undergraduate students the opportunity to work with world-renowned leaders of the regenerative medicine field as part of the 2014 SRF Summer Scholars Program.

SRF is again partnering with the Buck Institute for Research on Aging and the Wake Forest Institute for Regenerative Medicine (WFIRM). In addition, three new universities will be participating in the Summer Scholars Program this year.

The Centre for the Advancement for Sustainable Medical Innovation (CASMI) will be hosting SRF Summer Scholars at the University of Oxford and the University College London. And, student research will also be conducted at the Harvard Stem Cell Institute and Harvard School of Medicine.

Students interested in conducting research to combat the diseases of aging should visit We also invite you to forward the program flyer to any university, organization, or student you think might be interested in a paid regenerative medicine internship this summer.

The Foundation hit their November 2013 goal for $100,000 by the end of the year. Many thanks are due to to all of you whose donations helped to meet the impromptu matching funds that were assembled at the end of last year in response:

SENS Research Foundation Year-End Fundraising Campaign a Success

In November 2013, SRF announced our year-end fundraising campaign. We set a goal to raise $100,000 in a little over six weeks. You, our supporters, came through for us in an incredible way. Everyone at SRF was thrilled by the overwhelming response. We initially received 3 grants from the Methuselah Foundation, Jason Hope, and Fight Aging! Each offered to match the first $15,000 we raised. We then received an additional grant of $15,000 in December from Michael Cooper.

All in all, we raised over $105,000 in donations and matching grants. We are so grateful to everyone who helped make it possible for us to meet and even exceed our campaign goal. We would also like to thank our sustaining supporters, individuals who have arranged to donate to us monthly all year long to help fund our efforts to fight age-related disease. And of course thank you to all of our matching grant providers.

Watch your inbox throughout the coming months for exciting news about our plans to further expand the work of SENS Research Foundation. Our mission - to transform the way the world researches and treats age-related disease - can only be achieved with your continued support.

"We all want to live longer, healthier lives. In order to achieve this we need to change our approach to medicine. It's not just about treating, it's about preventing." - Jason Hope

Thank you again for all your support in 2013 and into the future.


Over the past few years Jason Hope has donated a sizable amount of money to fund aspects of the SENS research program aimed at developing the foundations of human rejuvenation therapies. As is the case for Peter Thiel, just as important as the funding at this comparatively early stage in the revolution in aging research is the fact that influential high net worth individuals are willing to give public support to this cause. The more people who speak out to say that it is only sensible to pursue human rejuvenation, and the state of science is plausible enough to fund aggressively right here and right now, the easier it is to persuade those who still waver on the fence. Hope is presently more outspoken in his public support of SENS research than Thiel, as you might be able to tell from his website, and the more of this the better I say.

The tipping point in public persuasion for longevity science in general will come in only a few years, I think, given that large players are becoming involved - but it might take longer for SENS research, as disruptive to the status quo of the broader field of aging research as it is. All sweeping, new and better ways of making progress are initially resisted, and SENS is no exception.

Jason Hope has been engaged in reaching out to the community these past months, as you can tell by the occasional article here, his support for the year end matching funds just past, a plethora of press releases, and the three-part item at Next Big Future quoted below. I am always very pleased to see people with far more leverage and influence than I wholeheartedly endorsing the work of the SENS Research Foundation and its allied labs and scientists - this remains all too rare an event:

SRF Ends the Long History of Aging

Alzheimer's, cardiovascular disease, diabetes, and other age-related diseases are expensive and dramatically reduce quality of life. The average couple can expect to pay $220,000 in medical expenses throughout their retirement. Age-related illnesses pepper the top ten causes of death in the United States. Despite all the time, money, and effort invested in the treatment of these diseases, scientists have not yet cured any of them.

Those who participated in the early days of the SENS Research Foundation hoped to develop a strategy to mitigate the signs of aging that cause misery and early death. SRF founders predicted that aging would come under medical control someday with advanced technologies, such as gene therapy, stem cell therapy, and immune stimulants.

The founders of the SENS Research Foundation also said they expected this to happen within your lifetime. SENS believes senescence is an engineering problem that they can fix through organized collaboration between the scientific community, policymakers, and the public. SRF aims to create and maintain collaborations that work toward ending the disability, misery and early death associated with the aging process.

The End of Aging is Near

Despite all the advances in medical science, man has yet to cure any age-related diseases. Heart disease, cancer, diabetes, and other illnesses continue to ravage our bodies while we grow old, despite the best efforts of our doctors and mountains of medicine.

The SENS Research Foundation, or SRF, hopes to change all that. Through continued collaborative research, education and outreach, SENS will continue to build the industry that permanently eradicates old-age diseases. SRF establishes a path that leads us from where we are today, a time where the scientific community has the wherewithal to lay out a detailed plan like this one, to a tomorrow when prototype therapies reduce the signs of aging in laboratory mice. Because mice experience many of the same aging processes as humans do, negligible senescence in humans is possible.

Reaching for negligible senescence through anti-aging strategies has real-world applications that go far beyond reducing wrinkles and sagging skin in old people. Age-related illnesses, like heart disease, cancer and diabetes are debilitating and expensive. The increases in cost and decrease of quality of life will become more profound as a growing number of people live longer. Without a clear-headed approach to negligible senescence, the aging process will cripple an increasing population worldwide.

SRF Continues Its Fight Against Aging

At its core, SRF is a research foundation. Scientists and administrators associated with the foundation conduct and coordinate research into developing the fundamental technologies capable of halting the aging process. SRF also funds research at universities around the world and in SENS own SRF Research Center in Mountain View, California.

The SRF Research Center houses their internal research laboratory, where their scientists perform advanced rejuvenation biotechnology research. The focus of this work is to address the root causes of aging on a molecular level in a systematic and comprehensive way. Currently, the work of the SRF Research Center focuses on the Mitochondrial Mutations Research Project, LysoSENS, and OncoSENS.

The Mitochondrial Mutations Research Project strives to correct time-related damage to the "powerhouse" of human body cells, mitochondria. Researchers with LysoSENS work towards clearing out the waste that accumulates in cells over time. The OncoSENS research objective is to make cancer mutations harmless.


Stem cell research will produce knowledge and technologies essential to future rejuvenation treatments: understanding exactly why stem cell populations decline in activity with age; producing unlimited immune cells to order; growing replacement tissues and undamaged stem cells of all types, perfectly matched to the patient; and more. Unlike most of the other foundation technologies needed to create rejuvenation of the old, applications of stem cell research need little in the way of a helping hand from philanthropic organizations like the SENS Research Foundation. Work on stem cells is broad, very well funded, and energetic field - all that is really needed at this point is the occasional reminder that researchers should be focused on the effects of aging on stem cells if they want to produce effective treatments for age-related disease.

There is too much of interest going on in stem cell research, regenerative medicine, and tissue engineering to do more than point out highlights and representative snapshots here and there. What were amazing advances ten years ago occur every week nowadays in laboratories around the world: growing tissues for specific organs; isolating and learning how to work with specific populations of stem cells that support one organ or another; spurring great feats of regeneration; transplanting stem cells cultured from the patient for therapeutic benefit.

Here are a few recent examples of new work in the field, collectively illustrative of where things stand: for each quoted below, dozens more passed by largely unremarked in the past months. It is a busy time in the life sciences, and these are the opening years of a transformative era.

Belgian clinic repairs bones with novel technique

The ground-breaking technique of Saint Luc's centre for tissue and cellular therapy is to remove a sugar cube sized piece of fatty tissue from the patient, a less invasive process than pushing a needle into the pelvis and with a stem cell concentration they say is some 500 times higher. The stem cells are then isolated and used to grow bone in the laboratory. Unlike some technologies, they are also not attached to a solid and separate 'scaffold'. "It is complete bone tissue that we recreate in the bottle and therefore when we do transplants in a bone defect or a bone have a higher chance of bone formation." The new material in a lab dish resembles more plasticine than bone, but can be molded to fill a fracture, rather like a dentist's filling in a tooth, hardening in the body.

Stem Cell Replacement for Frequent Age-Related Blindness

About four and a half million people in Germany suffer from age-related macular degeneration (AMD). It is associated with a gradual loss of visual acuity and the ability to read or drive a car can be lost. The center of the field of vision is blurry, as if covered by a veil. This is caused by damage to a cell layer under the retina, known as the retinal pigment epithelium (RPE). It coordinates the metabolism and function of the sensory cells in the eye. Inflammatory processes in this layer are associated with AMD and "metabolic waste" is less efficiently recycled. To date, there is no cure for AMD; treatments can only relieve the symptoms.

[Scientists] have now tested a new method in rabbits by which the damaged RPE cells in AMD may be replaced. The researchers implanted different RPEs which were obtained, among others, from stem cells from adult human donors. After four days, the researchers used tomographic methods to check whether the replacement cells had integrated into the surrounding cell layers. "The implanted cells were alive. That is a clear indication that they have joined with the surrounding cells." After one week, the implanted cell layer was still stable. Even after four weeks, tissue examinations showed that the transplant was intact.

Harvard scientists control cells following transplantation, from the inside out

[Scientists] can now engineer cells that are more easily controlled following transplantation, potentially making cell therapies, hundreds of which are currently in clinical trials across the United States, more functional and efficient.

"Regardless of where the cell is in the body, it's going to be receiving its cues from the inside. This is a completely different strategy than the current method of placing cells onto drug-doped microcarriers or scaffolds, which is limiting because the cells need to remain in close proximity to those materials in order to function. Also these types of materials are too large to be infused into the bloodstream."

Cells are relatively simple to control in a Petri dish. The right molecules or drugs, if internalized by a cell, can change its behavior; such as inducing a stem cell to differentiate or correcting a defect in a cancer cell. This level of control is lost after transplantation as cells typically behave according to environmental cues in the recipient's body. [The new] strategy, dubbed particle engineering, corrects this problem by turning cells into pre-programmable units. The internalized particles stably remain inside the transplanted cell and tell it exactly how to act, whether the cell is needed to release anti-inflammatory factors or regenerate lost tissue.


Back in the day, prior to the foundation of the SENS Research Foundation, the SENS rejuvenation research programs were first organized and funded under the auspices of the Methuselah Foundation. At the same time the Foundation also launched and promoted the Mprize for longevity science: a research prize that continues to this day in order to encourage and reward scientists who demonstrate improved degrees of healthy life extension in mice. A lot has changed since then - a great deal of progress in advocacy, and large shifts in the culture of the scientific community when it comes to research into aging and longevity, a lot of that spurred by the activities of the Methuselah Foundation.

At the present time the Methuselah Foundation focuses on speeding up tissue engineering of whole organs via the New Organ initiative, but also funds and coordinates a range of other projects - as well as remaining an influence behind the scenes in the course of the research and advocacy community. This arrived in my in-box today from the Foundation staff:

Methuselah in 2013

Thanks to you, we had a fantastic year at the Methuselah Foundation. On December 5th, we officially launched the New Organ Liver Prize at the World Stem Cell Summit (WSCS) in San Diego, and we're actively seeking title sponsorship to help us increase the $1 million prize purse. Last year, we kicked off a new partnership with Organovo to get 3D bioprinters into key labs at universities involved in regenerative medicine research. We also awarded several new grants, one to study the longevity of bowhead whales and another for research on personalized gene sequencing to improve chemotherapy treatment.

The First New Organ Prize

Many thanks to Bernie Siegel and the WSCS for hosting our launch of the $1 million New Organ Liver Prize, a five-year international competition to advance the field of tissue engineering and regenerative medicine. With gratitude to our generous donors, our invaluable board of advisors, and our prize development partners at the Institute of Competition Sciences, we're thrilled to be underway and currently sourcing teams to compete for the prize.

All the details on prize rules, team registration, partnerships, and more are now available at our brand new website. We'd love to hear what you think! You can also check out some recent media coverage on Popular Science and NBC News.

"New Parts for People"

At the WSCS in December, Methuselah CEO David Gobel gave a rousing plenary talk on the origins of New Organ. "Here's why we have the New Organ Liver Prize," Gobel said. "It seems to me species insanity that we would spend $200,000+ to restore a car like a Shelby Cobra, and yet all that car's creator Carroll Shelby could get were junkyard parts. His heart came from a dead person - it wasn't new. His kidney came from his wonderful son, but it wasn't new. And it didn't fit. None of these parts fit."

Watch the video.

A Year-End Gift to SENS

To close out the year, Methuselah put up $15,000 - alongside $15,000 from philanthropist Jason Hope and another $15,000 from Fight Aging! - in a 3:1 matching donation to our good friends at the SENS Research Foundation in support of their work advancing rejuvenation science.

Silverstone Merges with BiologixTx

Thanks to the support of Methuselah Foundation donors, Silverstone Matchmaker was able to take the kidney matching software it had developed for use in isolated Local Area Networks and transition it into the cloud, enabling an integrated network of hospitals to begin coordinating transplants through the platform. Now, as of November 2013, Silverstone has entered into an agreement with BiologicTx to further advance its distribution and development.

"The acquisition of Silverstone Solutions, combined with the addition of David Jacobs to the BiologicTx team, advances our commitment to Kidney Paired Donation and greatly expands our innovative technology platform immediately and in the future," said Darrin Carrico, President and Co-Founder of BiologicTx.

Last year alone, 61 lives were saved through Matchmaker-enabled paired kidney donations. We look forward to Silverstone's continued success and are grateful to our supporters for helping to make it possible.

Looking Ahead to 2014

We've got a lot planned for 2014, including the announcement of the first round of research teams planning to compete for the New Organ Liver Prize. Stay tuned also for news of our next New Organ Prize, an organ preservation competition currently in development with the Organ Preservation Alliance incubated by Singularity University Labs in Silicon Valley.

This year, we're also looking to finalize placements of 3D tissue printers in university research labs, so if you're involved in a project that would benefit from an Organovo printer, please let us know ASAP! Send a brief executive summary describing how you would use the printer to generate advances in organ engineering to Special consideration is being given to microvascular engineering to enable macro tissues in 3D.

Our New Website

In conjunction with our launch of the New Organ Liver Prize, we recently overhauled our main website, and we're proud of the results. If you haven't checked it out yet, please do! We'd love to know what you think.


Advocacy, philanthropy, and practical efforts aimed at breaking new ground in medical science tend to ebb and flow like the tide: initiatives come in waves, as it takes some time for communities to form, evolve, digest the results of the last wave, assess new knowledge, and for newly motivated leaders to realize their roles and step forward.

The current wave, of which the most visible organizations involved in advocacy are the Methuselah Foundation, SENS Research Foundation, and the Longevity Dividend (and its supporting organizations), started out in earnest a decade ago, give or take. Tens of millions of dollars have been raised and devoted to research aimed at human rejuvenation, and a billion dollars or more for unsuccessful attempts to develop and commercialize means to modestly slow aging. Concurrently, a great deal of networking behind the scenes has led to a research community that is much more receptive to the goal of enhancing human longevity.

The start of the present wave took place ten years after a much smaller set of initiatives were launched or set underway, came and went, such as the work of the late Robert Bradbury. The 1990s were a thin time to be interested in serious work on human longevity, and the broader research community was largely disinterested in showing any sort of public support for these ideas.

The tide is coming in these past few decades, however. The waves are growing greatly in size and strength from cycle to cycle: it doesn't happen anywhere near as rapidly as we would like, but it is happening. The wave of the 1990s raised and directed only a few million dollars in funding to forward-looking causes related to longevity science, and went largely unnoticed by the broader public - but the community of supporters and advocates was significantly larger by the end than at the beginning. Concurrently tens of millions went to research into the newly discovered plasticity of longevity and aging in laboratory species: genetic engineering to discover ways to extend life through metabolic manipulation. The wave of the past decade has raised at least ten times as much as these figures on either side of the divide (the radical goals of rejuvenation versus the mainstream focus on slowing aging), and made comparatively large inroads into public and scientific perception. The times are changing, and biotechnology is progressing rapidly. What looked like pipe dreams twenty years ago are practical postgraduate research projects today.

It is about time for the next wave to begin. One might even argue that the decision by Google's board to devote hundreds of millions of dollars to mainstream longevity research marks the opening of the next decade of advocacy and research aimed at extending the healthy human life span. Again, something that looks like a tenfold multiple of funding compared to the wave now ending might occur if Google follows through with the plan as sketched to date - though it isn't at all clear that Google's Calico initiative will do anything more than augment the National Institute on Aging (NIA), and to a first approximation the NIA isn't funding anything that will lead to radical life extension or human rejuvenation.

But a rising tide raises all boats: the more that targeted treatment of aging becomes a deliberately funded and discussed goal, the easier it becomes to raise funds for rejuvenation research along the lines of the SENS model of damage repair - work that can lead to radical life extension on a comparatively short timeframe, given sufficient resources and interest.

Beyond Google, we might expect to see all sorts of new initiatives launching in the next few years: people new to the community, emboldened by what they have seen in the research community and in the efforts of groups now a decade old. Welcome aboard to all of them, I say: the more the merrier. There is still a great deal to accomplish, and the more who help out the better our chances of attaining and benefiting from the goal of working rejuvenation treatments.


Monday, January 13, 2014

Mitochondria are important in aging, and the process by which they become damaged and contribute to degenerative aging starts with the fact that they emit reactive oxidants as a byproduct of their normal operation. The best approaches to removing this cause of aging involve repair of mitochondrial damage or altering cells to make the damage irrelevant, but researchers are also investigating ways to target antioxidants to the mitochondria. Additional antioxidants to augment natural ones soak up more of the oxidants and thus in theory slow down the pace of damage and the pace of aging. Studies carried out with plastinquinone mitochondrially targeted antioxidants seem to bear this out.

Mitochondrially targeted antioxidants are nowhere near as effective a strategy as repair, however. They cannot reverse or halt this contribution to aging, they can only somewhat slow it. But here is news of another type of mitochondrial antioxidant in early studies:

describe how in laboratory tests, they compared the protection offered against either UVA radiation or free radical stress by several antioxidants, some of which are found in foods or cosmetics. While UVB radiation easily causes sunburn, UVA radiation penetrates deeper, damaging our DNA by generating free radicals which degrades the collagen that gives skin its elastic quality.

The [team] found that the most potent anti-oxidants were those that targeted the batteries of the skin cells, known as the mitochondria. They compared these mitochondrial-targeted anti-oxidants to other non-specific antioxidants such as resveratrol, found in red wine, and curcumin found in curries, that target the entire cell. They found that the most potent mitochondrial targeted anti-oxidant was Tiron - 4,5-Dihydroxy-1,3-benzenedisulfonic acid disodium salt monohydrate - which provided 100%, protection of the skin cell against UVA sun damage and the release of damaging enzymes causing stress-induced damage.

Resveratrol, the antioxidant found in red wine, was found to protect against 22% of both the ultraviolet A radiation and stress-induced damage. NAC, a frequently used laboratory-based anti-oxidant, offered 20% protection against oxidative stress and 8% against UVA and curcumin offered 16% protection against oxidative stress and 8% against UVA. In comparison Tiron offered 100% protection against UVA radiation and 100% protection against oxidative stress

The team intends to take the work forward by further understanding the mechanism of how Tiron works, developing a compound similar to Tiron and testing for toxicity in humans. They say it will be several years before it is ready for use as a skin product or supplement.

If this interests you, bear in mind that other injected or ingested mitochondrially targeted antioxidants have far more work done on them, have more impressive effects at the cellular level, are shown to prevent or slow a range of age-related conditions, and yet still cannot extend life greatly in laboratory animals: 10% in flies, for example, far less than the extension of life obtained through calorie restriction.

Monday, January 13, 2014

Despite a long, slow trend upwards in life expectancy (at birth, as an adult, and for old people) there are still those researchers who believe that there are limits on human life span. This is on the one hand silly: the scientific community will in time overcome the causes of aging. On the other hand it is most likely true that there exist one or more slow degenerative processes still largely unaffected by modern medicine that kill everyone who survives all of the common causes of age-related death.

Based on autopsy data from supercentenarians, a good candidate for a present lifespan-limiting process in humans is the development of senile amyloidosis: misfolded proteins aggregate to clog the heart and blood vessels. But we can easily envisage ways to treat this condition, such as by training the immune system to destroy the errant proteins, as is presently under development in the Alzheimer's research community.

Aging and age-related death are composed of a laundry list of items that can all be tackled successfully by the near future of medical research: it's just a matter of prioritizing and funding the necessary work, something that at present the public and broader research community has little enthusiasm for, sadly.

The past 200 years have enabled remarkable increases in human lifespans through improvements in the living environment that have nearly eliminated infections as a cause of death through improved hygiene, public health, medicine, and nutrition. We argue that the limit to lifespan may be approaching. Since 1997, no one has exceeded Jeanne Calment's record of 122.5 years, despite an exponential increase of centenarians. Moreover, the background mortality may be approaching a lower limit.

We calculate from Gompertz coefficients that further increases in longevity to approach a life expectancy of 100 years in 21st century cohorts would require 50% slower mortality rate accelerations, which would be a fundamental change in the rate of human aging. Looking into the 21st century, we see further challenges to health and longevity from the continued burning of fossil fuels that contribute to air pollution as well as global warming. Besides increased heat waves to which elderly are vulnerable, global warming is anticipated to increase ozone levels and facilitate the spread of pathogens. We anticipate continuing socioeconomic disparities in life expectancy

Pessimism abounds in this age of ours that is characterized by wealth, plenty, and rapid, accelerating progress in technology and medicine. There is nothing new about that, of course. People have long been entranced by the false vision of doom ahead.

Tuesday, January 14, 2014

Researchers here suggest that primates - and humans especially - are comparatively long-lived among mammalian species because of differences in metabolism that lead them to burn fewer calories. There is a strong association between resting metabolic rate and longevity in mammals, although one should view this as an emergent property of other aspects of biology, such as the structure and operation of mitochondria, known to be important in aging. High metabolic rates also correlate with increased mortality within a species. This is interesting, but not really actionable when it comes to doing something about aging:

Most mammals, like the family dog or pet hamster, live a fast-paced life, reaching adulthood in a matter of months, reproducing prodigiously (if we let them), and dying in their teens if not well before. By comparison, humans and our primate relatives (apes, monkeys, tarsiers, lorises, and lemurs) have long childhoods, reproduce infrequently, and live exceptionally long lives. Primates' slow pace of life has long puzzled biologists because the mechanisms underlying it were unknown.

An international team of scientists working with primates in zoos, sanctuaries, and in the wild examined daily energy expenditure in 17 primate species, from gorillas to mouse lemurs, to test whether primates' slow pace of life results from a slow metabolism. Using a safe and non-invasive technique known as "doubly labeled water," which tracks the body's production of carbon dioxide, the researchers measured the number of calories that primates burned over a 10 day period. Combining these measurements with similar data from other studies, the team compared daily energy expenditure among primates to that of other mammals.

"The results were a real surprise. Humans, chimpanzees, baboons, and other primates expend only half the calories we'd expect for a mammal. To put that in perspective, a human - even someone with a very physically active lifestyle - would need to run a marathon each day just to approach the average daily energy expenditure of a mammal their size."

Tuesday, January 14, 2014

An interesting approach to the challenges of cartilage regrowth is outlined here:

Articular cartilage is the tissue that lines joints such as hips, knees and shoulders, providing cushioning and smooth movement. Similar to bones and muscles, cartilage only stays healthy and strong through loading, or applying force, through physical activity. Until recently, researchers did not know how cartilage converts mechanical loading into the ion channel signals that promote growth. Understanding how cartilage senses mechanical loading could equip researchers with the knowledge needed to prevent or better treat joint diseases.

"Mechanical loading plays a critical role in the overall health of the cartilage. If we can figure out how cartilage cells sense mechanical loads, we can trick them into thinking they are being exercised or stop them from responding to abnormal loading. Think of it as artificial exercise for your cartilage."

Researchers looked at articular cartilage cells from pigs and focused on TRPV4, an ion channel abundant in cartilage cells that can be turned on during mechanical loading. When the researchers "exercised" the cartilage cells using mechanical loading, the cells sensed the loading and grew cartilage tissue. When they added a compound that blocked TRPV4, essentially turning off signals from the ion channel, the cartilage did not grow and the effects of the mechanical loading were lost.

Next, the researchers substituted mechanical loading for a chemical that activated TRPV4. Without having to exercise the cartilage, they observed the growth of cartilage even more so than with the mechanical loading. The findings suggest that TRPV4 is responsible for sensing mechanical loading in the cartilage. Now that they know that turning on TRPV4 can simulate the effects of mechanical loading in cartilage cells, the researchers are looking at ways to harness this potential.

Wednesday, January 15, 2014

There is some debate over whether rapamycin extends life in mice by actually slowing aging or by merely reducing cancer risk. There will be more studies like this one in which researchers gather a great deal of data about the effects of rapamycin on epigenetic profiles and other detailed aspects of mouse biology:

Rapamycin was found to increase (11% to 16%) the lifespan of male and female C57BL/6J mice most likely by reducing the increase in the hazard for mortality (i.e., the rate of aging) term in the Gompertz mortality analysis. To identify the pathways that could be responsible for rapamycin's longevity effect, we analyzed the transcriptome of liver from 25-month-old male and female mice fed rapamycin starting at 4 months of age. Few changes ( less than 300 transcripts) were observed in transcriptome of rapamycin-fed males; however, a large number of transcripts (more than 4,500) changed significantly in females.

The male mice fed rapamycin were found to segregate into two groups: one group that is almost identical to control males (Rapa-1) and a second group (Rapa-2) that shows a change in gene expression (more than 4,000 transcripts) with more than 60% of the genes shared with female mice fed Rapa. 13 pathways were significantly altered in both Rapa-2 males and rapamycin-fed females with mitochondrial function as the most significantly changed pathway. Our findings show that rapamycin has a major effect on the transcriptome and point to several pathways that would likely impact longevity.

Wednesday, January 15, 2014

As interest grows in treating human aging and extending life, there is also a corresponding interest in investigating long-lived species so as to establish the factors that determine differing length of life. As a companion piece to last month's post on investigations into the biology of long-lived ocean quahog clams, the species Arctica islandica, here is another paper on the subject. This one focuses on teleomere biology, with results that are largely to be expected given other studies demonstrating a very consistent stability of metabolism across the potentially centuries-long life span of this species:

The shortening of telomeres as a causative factor in ageing is a widely discussed hypothesis in ageing research. The study of telomere length and its regenerating enzyme telomerase in the longest-lived non-colonial animal on earth, Arctica islandica, should inform whether the maintenance of telomere length plays a role in reaching the extreme maximum lifespan (MLSP) of more than 500 years in this species.

Since longitudinal measurements on living animals cannot be achieved, a cross-sectional analysis of a short-lived (MLSP 40 years from the Baltic Sea) and a long-lived population (MLSP 226 years Northeast of Iceland) and in different tissues of young and old animals from the Irish Sea was performed. A high heterogeneity of telomere length was observed in investigated A. islandica over a wide age range (10-36 years for the Baltic Sea, 11-194 years for Irish Sea, 6-226 years for Iceland). Constant telomerase activity and telomere lengths were detected at any age and in different tissues; neither correlated with age or population habitat.

Stable telomere maintenance might contribute to the long lifespan of A. islandica. Telomere dynamics are no explanation for the distinct MLSPs of the examined populations and thus the cause of it remains to be investigated.

Thursday, January 16, 2014

Here is yet another study to add to those demonstrating that physical activity is associated with a lower risk of chronic disease. Causality for this link is well demonstrated in laboratory animals, but human studies must use statistical methods on a population, or track large numbers of people for decades, which makes it more challenging to prove that exercise causes better health. Given the weight of evidence at this point, however, that exercise improves health is a good working assumption.

The paper for this study is open access and linked in the release materials quoted below:

People who decrease sitting time and increase physical activity have a lower risk of chronic disease. Even standing throughout the day - instead of sitting for hours at a time - can improve health and quality of life while reducing the risk for chronic diseases such as cardiovascular disease, diabetes, heart disease, stroke, breast cancer and colon cancer, among others.

The researchers studied a sample of 194,545 men and women ages 45 to 106. The data was from the 45 and Up Study, which is a large Australian study of health and aging. "Not only do people need to be more physically active by walking or doing moderate-to-vigorous physical activity, but they should also be looking at ways to reduce their sitting time." Sitting for prolonged periods of time - with little muscular contraction occurring - shuts off a molecule called lipoprotein lipase, or LPL. Lipoprotein lipase helps to take in fat or triglycerides and use it for energy.

"We're basically telling our bodies to shut down the processes that help to stimulate metabolism throughout the day and that is not good. Just by breaking up your sedentary time, we can actually upregulate that process in the body."

Thursday, January 16, 2014

Crowdfunding will be an important component of future medical research: it is the logical evolution of the efforts of past decades in which philanthropic foundations raised awareness and funding to accelerate research into treatments for specific diseases. Philanthropy has long been necessary to enable the most important early stage, high-risk research to move forward. Large, established institutional funding sources have little appetite for risk and consequently do very little to move the needle on efforts to create the next generation of medical technology.

This is all very important for the future of serious rejuvenation research, such as SENS-style efforts to repair the cellular and molecular damage that causes aging. This is presently a minority component of the minority field of aging research, neither well supported nor well known. It is, however, the future of medical research if nurtured - a disruptive titan in its earliest stages of growth. For that growth to occur there must be financial support and a community of supporters willing to take on the risks of early stage research. We should keep an eye on trends that may help this to come about.

The falling cost of communication means that intermediaries such as traditionally structured per-disease research foundations are becoming less necessary. They still play an important role in digesting information from the field and educating supporters, but it is now cost-effective for scientists to reach out directly, and for supporters to educate themselves to the point of being able to pick and choose exactly which projects they wish to fund. A new infrastructure is arising to build marketplaces and tools for this process, and Microryza is one of the initiatives in this space:

Luan and Wu are both young scientists - they're in their 20s - but their thinking was based on the old entrepreneurial approach: to be successful, find a hole and fill it. The particular hole they were dealing with is that scientists are often forced to siphon off months of precious time and incalculable amounts of creative energy as they focus on writing grant proposals. Worse, for all that investment in time and energy, they may have no success to show for it.

Fully 80% of Federal grant applications are never funded, and in biomedicine, the average age of a first-time grant recipient is 42. Too many projects never get funded because they seem risky, the proposer is young, the amount is too small to be worth the paperwork, or it's simply an approach that's never been tried before. As Luan says, "It's increasingly difficult for new ideas to get off the ground, especially the innovative, high-risk ideas with the biggest impact."

The answer to small-scale innovative scientific research funding could be to leverage the worldwide power of the internet to create a microfinance funding source involving individual subscribers. According to Luan, there's a lot researchers need to learn about public outreach if they're to make their scientific crowd-funding a success. "People wanting to do crowd funding may not be using Twitter or Facebook, and they may not know where to go to reach out to the communities that are passionate about their issue."

Friday, January 17, 2014

Autophagy is a collection of cellular housekeeping processes known to be important in aging: many of the methods of altering metabolism to extend life include raised levels of autophagy in their effects. Artificially boosting autophagy beyond normal levels - or even just restoring it to youthful levels, as it declines with age - has for some years shown promise as a method of treating a range of age-related conditions, especially those that involve aggregations of misfolded proteins. Here is an example of this sort of work:

Abnormal aggregation of SNCA/α-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a selective form of autophagy, while aberrant SNCA may act as a CMA inhibitor.

We summarize our recent data showing that induction of CMA, via overexpression of the protein controlling its rate-limiting step, the lysosomal receptor LAMP2A, effectively decreases SNCA levels and ameliorates SNCA-induced neurodegeneration, both in neuronal cell culture systems and in the rat brain. Such findings suggest that modulation of LAMP2A and, consequently, CMA, represents a viable therapeutic target for PD and other synucleinopathies where SNCA accumulation and aggregation plays a fundamental role.

Friday, January 17, 2014

The composition of gut bacteria is thought to influence aging: there is a modest range of work on this topic in laboratory animals, but nowhere near as much as on, say, the effects of calorie restriction on aging. Here is an example of ongoing investigations:

[Scientists] have promoted health and increased lifespan in Drosophila by altering the symbiotic, or commensal, relationship between bacteria and the absorptive cells lining the intestine. The research [provides] a model for studying many of the dysfunctions that are characteristic of the aging gut and gives credence to the growing supposition that having the right balance of gut bacteria may be key to enjoying a long healthy life.

The bacterial load in fly intestines increases dramatically with age, resulting in an inflammatory condition. The imbalance is driven by chronic activation of the stress response gene FOXO (something that happens with age), which suppresses the activity of a class of molecules (PGRP-SCs, homologues of PGLYRPs in humans) that regulate the immune response to bacteria. PGRP-SC suppression deregulates signaling molecules that are important to mount an effective immune response to gut bacteria. The resulting immune imbalance allows bacterial numbers to expand, triggering an inflammatory response that includes the production of free radicals. Free radicals, in turn, cause over-proliferation of stem cells in the gut, resulting in epithelial dysplasia, a pre-cancerous state.

[Researchers] increased the expression of PGRP-SC in epithelial cells of the gut, which restored the microbial balance and limited stem cell proliferation. This enhancement of PGRP-SC function, which could be mimicked by drugs, was sufficient to increase lifespan of flies. "If we can understand how aging affects our commensal population - first in the fly and then in humans - our data suggest that we should be able to impact health span and life span quite strongly, because it is the management of the commensal population that is critical to the health of the organism."

"Quite strongly" in this context means a couple of years in humans, or a few days in flies - a very minor, modest extension of life in the grand scheme of things, in other words. This is the trouble with most of present day research in the field: it aims only to slow aging, and only to slow aging a little. Ambitions are low, and this - and much of the rest of the field - certainly isn't SENS or otherwise at all relevant to a goal of radical life extension of decades or more.


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